Versatile Chiral Building Blocks by Catalytic C-H and C-C Activation

轴手性联芳基化合物在不对称反应中被广泛用作辅助配体，具有很高的对映选择性，是许多具有生物活性的天然产物的组成部分。虽然轴手性联芳基化合物是一个很有吸引力的合成靶点，但它们很难制备。现有方法的主要限制之一是底物范围有限，因此需要一种更通用的方法来合成轴手性双芳烯。为了开发这种方法，本项目将探索两种涉及催化C-C和C-H活化的方法。特别是，通过对联苯中的张力C-C键（图1，方案a）和联苯中的邻位C-H键（图2，方案B）进行C-C功能化，可以得到一系列功能化的双芳基。为了开发C-C功能化方法，一系列具有各种配体的钯、镍、铑和铱金属前体将在模型反应中进行初步测试，以确定最佳的催化体系。然后将通过用一系列硼烷、二硼烷和硅硼烷对联苯进行功能化试验来探索这种方法的范围。硼基或硅基取代的双芳基特别令人感兴趣，因为它们易于后续功能化，因此它们具有获得广泛底物范围的潜力。此外，具有多种r取代基的联苯将在反应中进行测试，以了解电子和立体构型对环开度的影响。在第二种方法C-H活化中，将使用过渡金属催化剂在邻位上使用导向基团来增加功能（图1）。方案B)。要探索的官能团包括硼基、硅基、炔基和氨基，同样地，因为它们易于后续功能化。这两种方法的手性诱导都是通过使用手性金属催化剂和在手性添加剂存在下的非手性金属催化剂来实现的。

Axially chiral biaryl compounds are of high importance as they are widely used as auxiliary ligands in asymmetric reactions giving high enantioselectivities and form a part of many biologically active natural products. Although axially chiral biaryl compounds are an attractive synthetic target, they are difficult to make. One of the main limitations to existing methods is a limited substrate scope, thus a more general method for the synthesis of axially chiral biaryls is needed. To develop such a method, two approaches that involve catalytic C-C and C-H activation will be explored in this project. In particular, a range of functionalised biaryls will be obtained by C-C functionalisation of strained C-C bonds in biphenylenes (Fig. 1, Scheme A) and ortho C-H bonds in biphenyls (Fig. 2, Scheme B). To develop the C-C functionalisation approach, a range of palladium, nickel, rhodium and iridium metal precursors with a variety of ligands will be initially tested in a model reaction to identify the best catalytic system. The scope of this approach will then be explored by trialling functionalisation of the biphenylenes with a range of boranes, diboranes and silaboranes. Boryl or silyl substituted biaryls are of particular interest because they are amenable to subsequent functionalisation, thus they have the potential to give access to a wide substrate scope. In addition, biphenylenes with a variety of R-substituents will be tested in the reaction to see what effect electronics and sterics have on the ring opening. In the second approach C-H activation, a directing group will be used to add functionality in the ortho position using a transition metal catalyst (Fig 1. Scheme B). The functional groups to be explored include boryl, silyl, alkynyl, and amino, similarly because they are amenable to subsequent functionalisation. Chirality induction in both approaches will be achieved by the use of chiral metal catalysts and achiral metal catalysts in the presence of chiral additives.